Human Studies

Osteoarthritis is a prevalent, debilitating, and costly chronic disease for which recommended first-line treatment is underused.

rheumatic diseases are the most frequent cause of non-malignant chronic pain. In recent years, pain and its management have become more important in rheumatology.

Temporomandibular pain (TMD) is a frequent symptom comprising pain around the mandibular jaw with a high dependence on stressors. Chronic pain has been associated with changes of the brains grey matter volume (GMV), but previous studies on GMV alterations associated with TMD have yielded contradictory results. This might be caused by divergent samples and study methods. We here tested GMV alterations using voxel based morphometry in three clinical samples (summing up to 47 TMD patients) and a population sample with 57 participants who indicated facial pain for the last 6 months. The GMV of pain patients was compared against age-matched and gender-matched participants without chronic pain (60 for the clinical sample comparison and 381 for the cohort sample comparison) who underwent the same assessments as the patient group (MRI measurements and data evaluation using CAT12). In a region of interest analysis, only the clinical samples showed an effect of decreased GMV in the anterior medial cingulate cortex reaching into the medial prefrontal cortex, known to be especially vulnerable for chronic pain grey matter volume reduction. The analysis of the population-based sample did not reveal relevant GMV differences. Overall, an important question remains as to whether most inconsistent results from VBM-studies in chronic pain are related to chance results facilitated by small sample size and selection of patient samples.

To better understand the mechanisms underpinning work-related neck pain, this cross-sectional and single-blinded study compared somatosensory profiles among sonographers with varied neck disability levels. Based on K-mean cluster analysis of scores on the neck disability index (NDI), participants were classified into no (NDI≤8%, n=31, reference group), mild (NDI=10%-20%, n=43) or moderate/severe (NDI≥22%, n=18) disability groups. Data were collected on bodily pain distribution and severity and psychological measures including depression, anxiety, pain-catastrophizing and fear-avoidance beliefs using validated scales. Participants attended one session of quantitative sensory testing performed according to a standardized protocol, including local and remote thermal and mechanical pain thresholds, temporal summation of pain (TSP), conditioned pain modulation (CPM) and an exercise-induced analgesia (EIA) paradigm. Compared to participants with no and mild disability, those with moderate/severe disability showed more widespread pain, cold and mechanical hyperalgesia at a remote non-painful site and significantly higher TSP. Participants with mild disability demonstrated significantly higher TSP than those with no disability. These group differences were attenuated after adjusting for depression or anxiety, indicating these psychological factors may mediate the somatosensory changes associated with neck disability. Group differences were not found for CPM or EIA. These findings suggest that heightened pain facilitation, rather than impaired pain inhibition may underpin nociplastic pain in participants with moderate/severe disability, and it may be associated with depression and anxiety. Clinicians should be aware that individuals with work-related neck pain presenting with moderate/severe disability display distinct somatosensory features and tailor management strategies accordingly.

To prevent pain associated with 8% capsaicin application, pretreatment with local anesthetics, such as EMLA (eutectic mixture of lidocaine 2.5% and prilocaine 2.5%), is considered an option. However, there is contradicting evidence regarding the effects of local analgesia on capsaicin-induced desensitization. In session 1, two skin areas in each forearm of 24 healthy volunteers were randomized to 2-hour pretreatment with EMLA/placebo cream. After pretreatment, 8% capsaicin patches were applied for 3 hours in one placebo and one EMLA pretreated area, obtaining the following four areas: Capsaicin+EMLA, Capsaicin+Placebo, EMLA alone, and Placebo. Pain intensity scores were assessed during the 3-h application of capsaicin. Warmth detection, heat pain sensitivity, and micro-vascular reactivity were measured after the removal of capsaicin. After 24 hours, in session 2, all tests were repeated followed by histamine application in each area to examine itch intensity and neurogenic flare. Overall, EMLA caused significant reductions in capsaicin-induced pain compared with placebo (p=0.007) and enhanced the capsaicin-induced increase in superficial blood perfusion immediately after the 3-hour capsaicin application (p<0.01). Regardless of pretreatment, capsaicin induced heat hyperalgesia immediately after the application (p<0.001). 24 h post application, heat pain sensitivity was normalized. However, WDT increased significantly (p<0.001). Capsaicin tended to reduce the itch intensity and significantly reduced the neurogenic flare (p<0.05) induced by histamine compared with EMLA alone. The findings suggest that pre-treatment with topical analgesic cream reduces application site pain without interfering with the 8% topical capsaicin-induced desensitization. Perspective: Pretreatment with local anesthetic EMLA cream might be considered a good therapeutic option to reduce the pain associated with 8% capsaicin application currently used for treatment of neuropathic pain syndromes. This study also suggests the existence of a synergistic effect of capsaicin and EMLA on the process of neurogenic inflammation.